title: Riociguat for the treatment of pulmonary hypertension.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed.
  
  
  METHODS
  This review will help readers understand the mechanism of action of the soluble guanylate cyclase (sGC) stimulator riociguat (BAY 63-2521) and will provide a comprehensive summary regarding efficacy and safety of this drug in the management of PH. The most relevant publications up to December 2010 were used as sources for this review.
  
  
  CONCLUSIONS
  Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany. ralph.schermuly@uglc.de
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.forename: Wiebke
authors.initials: W
authors.lastname: Janssen
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.forename: Johannes-Peter
authors.initials: JP
authors.lastname: Stasch
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Hossein Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006162:Guanylate Cyclase; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008955:Models, Cardiovascular; D011720:Pyrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D000071756:Soluble Guanylyl Cyclase
chemical_list: D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat